Treatment of rats with poly ADP-ribose inhibitors such as nicotinamide, after 90% pancreatectomy results in pancreatic regeneration and amelioration of diabetes. Terazono and coworkers have shown that the regenerating pancreas greatly overexpresses a gene designated REG, which encodes for a novel 165 amino acid protein. In addition, recent studies have shown that AEG expression may parallel islet physiology. REG gene mRNA has been shown to be undetectable when endogenous insulin synthesis is suppressed, and to be restored when endogenous insulin synthesis is normalized. We hypothesize that REG may be a crucial autocrine and/or paracrine growth factor during embryogenesis as well as for maintenance of B-cell function in the adult. Therefore, we believe that alterations of the REG gene expression may be involved in the progressive B-cell dysfunction with aging and diabetes. We plan to use molecular techniques to measure mRNA levels of REG in the pancreas of rodents during the normal aging process, and in rodent strains with genetic forms of type I diabetes (NOD mouse, BB rat), and type II diabetes (db/db mouse, fa/fa rat).